Anti‑PD‑1 with a postbiotic for advanced, treatment‑naïve cutaneous melanoma

Anti PD-1 Plus Postbiotic Versus Anti PD-1 Alone in Locally Advanced or Metastatic, Treatment naïve, Cutaneous Melanoma: a Phase II Randomized Study With Correlative Biomarkers' Analysis:

This trial will test whether adding a postbiotic to anti‑PD‑1 immunotherapy helps boost tumor immune markers and improve outcomes in people with untreated stage IIIC or IV cutaneous melanoma.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 35 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Azienda Ospedaliera di Perugia (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 5 sites (Bari, BA and 4 other locations)
• Trial ID: NCT07050940 on ClinicalTrials.gov

What this trial studies

This is a calibrated, non‑comparative phase II trial that assigns patients with unresectable stage IIIC or IV cutaneous melanoma to receive standard anti‑PD‑1 therapy alone (calibration group) or anti‑PD‑1 plus a defined postbiotic (experimental group). The primary biological endpoint is upregulation of MHC class I antigen‑processing machinery in tumor cells, measured on baseline and on‑treatment tumor samples. Key clinical endpoints include overall response rate and progression‑free survival, with the calibration arm providing internal benchmark data to interpret activity in the experimental arm. Multiple Italian centers will enroll patients who have measurable disease and are willing to provide or undergo tumor biopsy.

Who should consider this trial

Good fit: Adults (≥18) with histologically confirmed unresectable stage IIIC or IV cutaneous melanoma who are treatment‑naïve for metastatic disease, have ECOG 0–1, at least one measurable lesion, and are willing to provide tumor tissue are ideal candidates.

Not a fit: Patients who have already received systemic therapy for metastatic disease, have poor performance status, have non‑cutaneous melanoma subtypes, or are unwilling/unable to provide tumor tissue may not benefit or be eligible.

Why it matters

Potential benefit: If successful, the combination could increase tumor antigen presentation and improve response rates and progression‑free survival with anti‑PD‑1 therapy.

How similar studies have performed: Early translational and clinical work has linked the gut microbiome and bacterial metabolites to better responses to immune checkpoint inhibitors, but using a defined postbiotic as a coadjuvant in this setting remains largely novel with limited direct clinical trial evidence.

Eligibility criteria

Inclusion Criteria:

* Patients 18 years or older
* Histologically confirmed, unresectable stage IIIC or IV metastatic melanoma;
* Eastern Cooperative Oncology Group performance status of 0 or 1;
* The patient must treatment naïve for metastatic disease
* Patients who have received anti-PD-1 therapy or anti BRAF/MEK in adjuvant setting and relapsed after 6 months of ending adjuvant therapy are allowed to enter clinical study.
* Patient has at least one measurable lesion that qualifies as a target lesion based on RECIST 1.1. Tumor lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, are not considered measurable unless there has been demonstrated progression in the lesion.
* Patient is willing to undergo a pretreatment tumor biopsy or provide qualifying archival tumor tissue. To qualify, archival tissue must have been sampled after last exposure to any systemic anti-neoplastic agent (including TVEC or anti-PD-L1 therapy whichever is last). Patients unable to undergo a biopsy may be enrolled if risk/benefit ratio of biopsy is considered unfavorable and/or when a biopsy would likely lead to significant delays in care. This decision must be accompanied by supporting documentation from the Investigator and performed in consultation with Medical Monitor. All pretreatment tissue must have been collected no more than 120 days prior to screening.
* Patient has recovered from the effects of any previous chemotherapy, immunotherapy, other prior systemic anticancer therapy, radiotherapy, and/or surgery (ie, residual toxicity no worse than Grade 1 \[Grade 2 treatment-associated peripheral neuropathy and/or any grade of alopecia are acceptable assuming all other inclusion criteria are met\]).
* Patient who has received prior systemic anti-neoplastic agent(s) must wait at least 5 half-lives or 4 weeks (whichever is shorter) following prior therapy before enrollment into the study, or 4 weeks if the half-life of a given investigational agent is not known.
* Patient has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 within 5 days before the first dose of study drug and an estimated life expectancy of at least 3 months.
* Patient has adequate hematologic reserve as evidenced by:

Absolute neutrophil count (ANC) of ≥1000/μL, Absolute lymphocyte count of

≥500/μL, Platelet count of ≥75,000/μL, and Hemoglobin of ≥9 g/dL (patients may be transfused to this level, if necessary, but transfusion must occur \>1 week prior to the first dose of study drug).

* Patient has adequate hepatic function as evidenced by aspartate transaminase and alanine transaminase values ≤3 × the upper limit of normal (ULN) and serum total bilirubin values of ≤1.5 × ULN (≤2 × ULN for patients with known Gilbert's syndrome) for the reference laboratory measured within 7 days prior to the first dose of study drug. For patients with documented baseline liver metastasis, the following limits will apply: 5 × ULN for transaminase and 2 × ULN for bilirubin.
* Patient has adequate renal function as evidenced by a serum creatinine ≤1.5 × the ULN for the reference laboratory or a calculated creatinine clearance of ≥45 mL/min by the Cockcroft-Gault Equation measured within 7 days prior to the first dose of study drug.
* Patient has international normalized ratio (INR) AND/OR prothrombin time (PT) AND activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless the patient is receiving anticoagulant therapy, in which case INR and/or PT and aPTT must be within the desired therapeutic range of intended use for such anticoagulants.
* Patient agrees to abide by the contraceptive requirements detailed in the protocol.
* Women of childbearing potential (WOCBP) must have a negative pregnancy test (serum or urine) within 3 days before the first dose of study drug (see the protocol for the definition of WOCBP).
* Life expectancy more than 3 months
* Presence of instrumentally or clinically measurable or evaluable lesions Informed consent obtained

Exclusion Criteria:

* Patients with mucosal or with a primary ocular melanoma
* Active symptomatic or asymptomatic brain metastases
* Patients with the following disorders: active, known, or suspected autoimmune disease (except for some non-serious disorders, such as vitiligo and type 1 diabetes mellitus, as specified in the study protocol);
* Previous malignancies (exceptions skin basocellular or squamocellular carcinoma radically resected, in situ uterine cervix in situ carcinoma radically resected) in the previous 2 years.

Where this trial is running

Bari, BA and 4 other locations

• Bari University-Oncologia medica — Bari, Ba, Italy (Not_yet_recruiting)
• Torino University-Le Molinette — Torino, To, Italy (Not_yet_recruiting)
• IRCCS Papa Giovanni II Bari — Bari, Italy (Not_yet_recruiting)
• INT Milano — Milan, Italy (Not_yet_recruiting)
• AO Perugia — Perugia, Italy (Recruiting)

Study contacts

• Principal investigator: Mario Mandalà, MD — AO perugia-University of perugia
• Study coordinator: Mario Mandalà, MED

Conditions Melanoma Metastatic; melanoma stage IIIC or IV; untreated for metastatic disease